FRAXA Research Foundation Works To Provide Hope To Families Struggling To Raise A Child, Or Children, With Fragile X Syndrome

FRAXA Research Foundation
is a parent run organization that funds research to find effective
treatments and, ultimately, a cure for Fragile X. Fragile X is the leading
inherited cause of mental retardation and the most common genetic cause of
autism.

Fragile X is caused when a gene fails to produce a single protein
necessary for normal brain function. There is a 50% chance of inheriting
the Fragile X gene when one parent is a carrier. As parents of children
with Fragile X, we understand first-hand the stress Chris Benoit and his
wife might have been coping with. At birth many children with Fragile X
seem normal and are often not diagnosed until two or three years of age
when the child fails to meet typical developmental milestones. The initial
shock of learning that your child is mentally impaired, followed by the
continued emotional and financial strain of finding appropriate schools,
child care and therapies can be an overwhelming emotional and financial
burden for many families. Some of the symptoms Fragile X can cause are —
severe anxiety, impaired learning, debilitating sensory integration
problems, very limited (or possibly no) speech, obsessive compulsive
behaviors, and even seizures — making day-to-day life extremely
challenging. Most children with Fragile X have a normal life expectancy
creating an added burden on parents to plan for their child’s future.

FRAXA funds biomedical research, in the US and internationally, aimed
at treating and curing Fragile X. Currently FRAXA has numerous treatments
for Fragile X in development in collaboration with pharmaceutical companies
worldwide. FRAXA’s basic research, like the recently announced therapeutic
potential of PAK inhibition, points the way toward innovative drug
therapies for Fragile X and related disorders like autism.

According to the Centers for Disease Control, FXS affects 1 in 4,000
males and 1 in 6,000 females of all races and ethnic groups. The prevalence
of autism ranges from 1 in 500 to 1 in 166 children. Currently there is no
effective treatment for FXS and other types of autism.

FRAXA Research Foundation
fraxa

UNICEF Rapid Response Team On The Ground In Samoa

A team of six emergency personnel are currently conducting rapid assessments in Samoa to ensure that the urgent needs of children are met following the earthquake and tsunami that struck the Pacific Island nation on Tuesday, September 29.

UNICEF Pacific Representative, Dr. Isiye Ndombi said “From experience, UNICEF knows that in an emergency, children are the most affected. It is therefore essential they have access to clean water, proper sanitation facilities, are protected from vaccine-preventable diseases such as measles and are able to resume education.”

“Our key relief priorities and response are in the areas of water and sanitation, health, education and protection,” he said.

The team arrived Thursday 1 October in Apia together with initial emergency supplies of 2000 Oral Re-hydration Salts, 5000 Water Purification Tablets and 7000 sets of communication materials promoting basic health practices in emergencies. On Saturday’s flight from Fiji to Samoa, UNICEF Pacific additionally sent 14 Early Childhood Development kits and 10 Enhanced Recreational kits.

“We will be sending further supplies tomorrow which include 3500 collapsable water containers (each holding 10 litres of water) and 5000 soap.”

UNICEF is closely working with the Government of Samoa and other UN agencies to provide assistance for up to 10-15,000 people. It is estimated that at least 9,000 children are affected.

The latest update on the number of tsunami victims shows 135 deaths, 310 injured and 3,500 displaced people including up to 2,000 displaced girls and boys.

Source
UNICEF

First Complete Surgical System Specifically Designed To Treat Progressive Osteoarthritis Of The Knee Is Launched In Europe

DePuy Orthopaedics EMEA announces the introduction of Sigma® High Performance Partial Knee, the only partial knee replacement system designed to provide the complete solution to progressive osteoarthritis in active patients.

Until now, orthopaedic surgeons have had limited options for the treatment of progressive degradation of the knee joints (osteoarthritis) in active patients who require care, but are not yet ready for a total knee replacement. The new high function, low wear Sigma® High Performance Partial Knee has been specifically designed to meet the needs of this important and growing patient population. The system enables surgeons to repair only the parts of the knee that are damaged and further parts can be added if the disease progresses. This allows for patients to achieve full function and pain relief at all stages of this degenerative disease.

“Sigma® High Performance Partial Knee is a major step forward for the growing number of active patients in their 40s and 50s requiring knee surgery”, comments Professor David Barrett, Consultant Orthopaedic Surgeon, Southampton University Hospital, UK. “The profile of knee replacement patients in Europe is changing, with patients getting younger and living more active lifestyles, the technological demands on the devices are increasing. It is important that we are now able to provide active patients with a surgical solution better suited to their lifestyle and expectations.”

Sigma® High Performance Partial Knee is the first truly modular system specifically designed to allow uni-compartmental, bi-compartmental or staged replacement* of the knee joint, meaning surgeons can match the implant specifically to a patient’s disease state. Now joint repair can be targeted so that healthy bone, cartilage and ligaments remain intact. The preservation of the natural tissues around the treated knee allows for a high level of movement, enabling most patients to carry on with active working and social lives post surgery.

Osteoarthritis is a common and disabling disease. Sigma® High Performance Partial Knee is expected to be welcomed by surgeons across Europe as with lengthening life expectancies and ageing populations, the condition is set to become the fourth leading cause of global disability by 2020.[1] An increasing trend seen is joint damage and degradation in younger people. In the UK for example, approximately a fifth of people aged 45-64 years old suffer osteoarthritic knee pain, and an estimated quarter of adults greater than or equal to 50 years old report disability from severe knee pain.[2]

“The availability of DePuy’s new partial knee system is important. It addresses an unmet need for a growing number of patients who only require partial knee replacement to ensure relief from the pain and discomfort of a total knee replacement”, notes Dr Florian Gottsauner-Wolf, Department of Orthopaedics, Landesklinikum Krems, Austria.

Notes

Sigma® High Performance Partial Knee

Sigma® High Performance Partial Knee is the only system specifically designed to address osteoarthritis in one or more compartments of the knee with compatible implants (patello-femoral and unicondylar). It is a modular system allowing surgeons to match the implant specifically to a patient’s disease state.

*Sigma® High Performance Partial Knee uni-compartmental, bi-compartmental or staged replacement means surgeons need only replace the part of the knee affected by disease and, if necessary, further parts can be added if disease progresses.

About osteoarthritis

Osteoarthritis is a progressive condition characterised by loss of joint cartilage that leads to pain and loss of function primarily in the knees and hips.[1] Patients typically experience; joint pain, tenderness, movement limitation, occasional effusion (fluid) and variable degrees of local inflammation.[1]

According to the World Health Organization, osteoarthritis is the most common type of arthritis or degenerative joint disease in the world, and a leading cause of chronic disability.[3] The prevalence of osteoarthritis increases indefinitely with age, as the condition is irreversible.[1]

[1] Woolf AD, Pfleger B. Burden of major musculoskeletal conditions. Bulletin of the World Health Organization 2003. 81 (9): 646:656. Available here. Last accessed June 2010

[2] NHS Clinical Knowledge Summaries. Available here. Last accessed June 2010

[3] WHO. Priority Medicines for Europe and the World. Available here. Last accessed June 2010

Source:

DePuy Orthopaedics

VIDA Diagnostics Gains FDA Approval For Comprehensive Lung Analysis Software

VIDA Diagnostics Inc. announced that its primary product, Pulmonary Workstation 2.0 (PW2) has obtained FDA 510(k) clearance for sale.

PW2 is the first commercial release of lung image analysis software from VIDA and comprises a comprehensive approach to quantitative, repeatable lung measurements including the industry’s first so-approved automatic lobe density and airway system measurement functions.

“We are privileged to be given the opportunity to make our leading PW2 application available to assist in the evaluation of millions of chronic obstructive pulmonary disease (COPD) and emphysema patients throughout the U.S.,” said John Garber, VIDA CEO. “Since these diseases often affect specific regions of the lung, the ability to individually and objectively measure each of the five lobes and 25 major airways should fast become an invaluable complement to existing systemic measures like pulmonary function tests.”

VIDA’s PW2 takes the complex information from a CT (computed tomography) scan of the lung and converts it into useful 3D images and measurements that are easily viewed by the practicing pulmonologist at the point of patient service, or by the radiologist in the radiology department. PW2 features include a number of lung or lobe volume and density measurements, an extensive named airway map and a full suite of measurement tools for each airway. For the first time, airway, lung, and lobe measurement tools are combined with advanced airway visualization to aid in patient assessment and procedure planning.

“With installations at 27 top research sites processing over 10,000 CT scans in the last three years, PW2 has proven to be a very reliable software package,” said Juerg Tschirren, VIDA Vice President of Engineering. “After extensive validation and testing, we are pleased to release our software, Pulmonary Workstation 2.0, for clinical use.”

VIDA Diagnostics Inc.
vidadiagnostics

American Lung Association Launches Retro Marketing Initiative To Support 2009 Christmas Seals(R) Campaign

The American Lung Association launched a new retro marketing initiative today to support its 2009 Christmas Seals Campaign, the year-end holiday fundraising drive that’s been raising money to support the charity’s fight for healthy lungs and healthy air for more than a century. While for-profit companies have had proven success in recent years using vintage packaging to sell products like cards, cereal and soft drinks, the Lung Association has developed a flashback branding campaign to boost year-end fundraising with the theme, “Celebrate Another Year.”

The Christmas Seals Campaign is the nation’s oldest direct-mail fundraising campaign, which began in 1907 to combat tuberculosis. In fact, a survey conducted by the Lung Association found that 60 percent of Americans are aware of Christmas Seals, and that this awareness correlates strongly with age: older Americans have greater familiarity.

“We’re hoping that this campaign will appeal not only to older Americans, who remember ‘licking and sticking’ their first Christmas Seal, but also to a younger demographic, who may not have heard of Christmas Seals but are attracted to all things vintage,” said Charles Connor, President and CEO of the American Lung Association.

Today, the Lung Association remains the third largest nonprofit mailer, and fights new battles against influenza, asthma, tobacco use, lung cancer and air pollution. This year, it will send Christmas Seals – decorative stamps used to decorate holiday cards and packages – to over 11 million households from October to December. In return, people send in contributions, which last year, brought in 35 percent of the charity’s total direct mail revenue.

The last time the American Lung Association supported the Christmas Seals Campaign with advertising was in 1996. This year, in a creative effort to appeal to people’s sense of nostalgia, the American Lung Association, brought three historic Christmas Seals to life in 15-, 20- and 30-second television public service advertisements, which will be distributed nationwide in mid-October, and can be viewed on ChristmasSeals. The charity also developed print and radio public service advertisements.

“We continue to be thankful for the loyalty of our Christmas Seals supporters, many of whom have given year-after-year for several decades, and in some cases, for half a century,” continued Connor. “While we hope that this new marketing push re-energizes our existing mail donors, we also hope to introduce Christmas Seals to a new generation of supporters via the web,” said Connor.

Even though, according to the U.S. Postal Service, Americans sent nearly 20 billion pieces of mail last holiday season, more and more people are choosing to send holiday greetings online. So for the first time this year, people can visit ChristmasSeals to view over one hundred years of Christmas Seals that they can either send in an e-card to friends or loved ones. Additionally, a Facebook application was developed so people can collect and share Christmas Seals with their social network.

Also new this year is an array of Christmas Seals gift merchandise. Vintage products include wrapping paper, adhesive gift tags, lapel pins and holiday ornaments. The items are sold individually and cost between $5 and $12.95. The charity is featuring a unique gift, “Christmas in a Box,” which retails for $75 and features a collection of Christmas Seals merchandise at a 20 percent discount. Proceeds from the sale of all these items will help support the mission of the Lung Association.

Throughout its history, the American Lung Association’s Christmas Seals campaign has been supported by celebrities and entertainers ranging from Bob Hope to the Smothers Brothers. Leading the charge as the 2009 National Celebrity Christmas Seals Chairperson is actress S. Epatha Merkerson, an Emmy, Golden Globe and SAG Award winner, Ms. Merkerson has won critical acclaim for her brilliant work in theatre, television and film, but is probably best known for her role as Lt. Anita Van Buren on NBC-TV’s “Law & Order.”

For more information on the American Lung Association’s Christmas Seals Campaign, visit ChristmasSeals, or call Carrie Martin 202-420-1141.

Source
American Lung Association

Abbott Announces HUMIRA® (adalimumab) Approved In Japan For The Treatment Of Rheumatoid Arthritis

Abbott announced that it has received approval from the Japanese Ministry of Health, Labour and Welfare for HUMIRA® (adalimumab) for the treatment of rheumatoid arthritis in patients with inadequate response to conventional therapy. This approval is the first for HUMIRA in Japan, where Abbott co-developed and will co-market HUMIRA with Eisai Co., Ltd. HUMIRA is now approved in 75 countries for rheumatoid arthritis and other autoimmune disease indications.

“The approval of HUMIRA in Japan is a significant milestone for Abbott,” said Glenn Warner, vice president, Pharmaceuticals, Japan, Abbott. “This approval is both good news for Japanese patients and a significant step forward for Abbott in Japan.”

HUMIRA is expected to become available to patients in Japan in the coming months, following the standard pricing approval process.

“The clinical studies of HUMIRA in Japanese patients demonstrated the efficacy and safety of this medicine,” said Prof. Nobuyuki Miyasaka, M.D., Department of Collagen Disease and Rheumatology, Tokyo Medical and Dental University Graduate School of Medicine, who was involved in the development of HUMIRA for the treatment of rheumatoid arthritis in Japan.

Abbott has submitted an application for approval of HUMIRA for plaque psoriasis, and is also developing HUMIRA in Japan for Crohn’s disease, ankylosing spondylitis, juvenile rheumatoid arthritis and ulcerative colitis. Eisai is co-developing and will jointly market these indications with Abbott.
More Information About Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, joint pain and stiffness, which can lead to long-term joint damage. The joints most commonly affected early in the disease are the smaller joints of the fingers, feet and wrists. The elbows, knees, ankles and hips can also be affected. Although there is no cure for RA, people continue to seek treatments that help alleviate pain and inflammation and slow disease progression.

More information on RA and current treatment options can be found at RA.

Important Safety Information

Globally, prescribing information varies; refer to the individual country product label for complete information.

Serious infections, sepsis, rare cases of tuberculosis (TB), and opportunistic infections, including fatalities, have been reported with the use of TNF antagonists, including HUMIRA. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease could predispose them to infections. Patients must be monitored closely for infections, including tuberculosis, before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should be discontinued if a patient develops a new serious infection until infections are controlled. Physicians should exercise caution when considering use of HUMIRA in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.

TNF-blocking agents have been associated with reactivation of hepatitis B (HBV) in patients who are chronic carriers of the virus. Some cases have been fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating HUMIRA.

The combinations of HUMIRA and anakinra as well as HUMIRA and abatacept is not recommended.

TNF antagonists, including HUMIRA, have been associated in rare cases with demyelinating disease and serious allergic reactions. Rare reports of pancytopenia including aplastic anemia have been reported with TNF-blocking agents. Adverse events of the haematologic system, including medically significant cytopenia have been infrequently reported with HUMIRA.

More cases of malignancies including lymphoma have been observed among patients receiving a TNF antagonist compared with control patients in clinical trials. The size of the control group and limited duration of the controlled portions of studies precludes the ability to draw firm conclusions. Furthermore, there is an increased background lymphoma risk in rheumatoid arthritis patients with long-standing, highly active, inflammatory disease, which complicates the risk estimation. During the long-term open-label trials with HUMIRA, the overall rate of malignancies was similar to what would be expected for an age-, gender- and race-matched general population. With the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF antagonist cannot be excluded. All patients, and in particular patients with a medical history of extensive immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, should be examined for the presence of non-melanoma skin cancer prior to and during treatment with HUMIRA.

In clinical studies with another TNF antagonist, a higher rate of serious congestive heart failure (CHF) related adverse events including worsening CHF and new onset CHF have been reported. Cases of worsening CHF have also been reported in patients receiving HUMIRA. Physicians should exercise caution when using HUMIRA in patients who have heart failure and monitor them carefully. HUMIRA should not be used in patients with moderate or severe heart failure.

The most frequently reported adverse event (?‰?1/10 patients) at least possibly causally related to HUMIRA is injection site reaction (including pain, swelling, redness or pruritus). Other common adverse events (?‰?1/100 patients) at least possibly causally related to HUMIRA include lower respiratory infections (including pneumonia, bronchitis), viral infections (including influenza, herpes infections), candidiasis, bacterial infection (including urinary tract infections), upper respiratory infection, dizziness (including vertigo), headache, neurologic sensation disorders (including paraesthesias), cough, nasopharyngeal pain, diarrhea, abdominal pain, stomatitis and mouth ulceration, nausea, hepatic enzymes increased, rash, pruritus, musculoskeletal pain, pyrexia and fatigue (including asthenia and malaise).

About HUMIRA

HUMIRA is the only fully human monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn???s disease and plaque psoriasis (Ps) in the United States and Europe. HUMIRA is also approved for the treatment of juvenile idiopathic arthritis (JIA) in the United States, and review for JIA in Europe is ongoing. Clinical trials are underway evaluating the potential of HUMIRA in ulcerative colitis. To date, HUMIRA has been approved in 75 countries and more than 250,000 people worldwide are currently being treated with HUMIRA.

HUMIRA resembles antibodies normally found in the body. It works by blocking tumor necrosis factor alpha (TNF-?±), a protein that, when produced in excess, plays a central role in the inflammatory responses of many immune-mediated diseases.

In the United States, HUMIRA is approved by the FDA for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis (RA). HUMIRA can be used alone or in combination with methotrexate (MTX) or other disease-modifying anti-rheumatic drugs (DMARDs). HUMIRA is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 4 years of age and older. HUMIRA can be used alone or in combination with MTX. HUMIRA is indicated for reducing the signs and symptoms of active arthritis, inhibiting the progression of structural damage and improving physical function in patients with psoriatic arthritis. HUMIRA can be used alone or in combination with MTX or other DMARDs. HUMIRA is indicted for reducing signs and symptoms in patients with active ankylosing spondylitis. HUMIRA is indicated for reducing the signs and symptoms and inducing and maintaining clinical remission in adults with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab. HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy of phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

In Europe, HUMIRA, in combination with MTX, is indicated for the treatment of moderate to severe, active RA in adult patients when the response to DMARDs including MTX has been inadequate, and for the treatment of severe, active and progressive RA in adults not previously treated with MTX. HUMIRA can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. HUMIRA has been shown to reduce the rate of progression of joint damage as measured by x-ray and to improve physical function, when given in combination with MTX.

Also in Europe, HUMIRA is indicated for the treatment of active and progressive PsA in adults when the response to previous DMARD therapy has been inadequate and for the treatment of severe, active AS in adults who have had an inadequate response to conventional therapy. HUMIRA is indicated for treatment of severe, active Crohn’s disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. For induction treatment, HUMIRA should be given in combination with corticosteroids. HUMIRA can be given as monotherapy in case of intolerance to corticosteroids or when continued treatment with corticosteroids is inappropriate. HUMIRA is indicated for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or PUVA.

Abbott’s Commitment to Immunology
Abbott is focused on the discovery and development of innovative treatments for immunologic diseases.

About Abbott

Abbott ( NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 68,000 people and markets its products in more than 130 countries. Abbott employs 2,100 people in Japan with offices in Tokyo, Osaka, Fukui, and Chiba.

Abbott
abbott

View drug information on Humira.

Alzheimer’s Disease: Newly Found Peptide Offers Hope Of Early Test And Better Treatment

Researchers in Japan have detected a peptide in cerebrospinal fluid (CSF) that can show whether a person is developing Alzheimer’s disease. Measuring the level of this peptide could show that the disease process has started, long before any serious damage is done to the brain.

This research, published in the journal EMBO Molecular Medicine, raises new opportunities for combating Alzheimer’s disease. Currently treatments can only be started after considerable structural damage has occurred in the person’s brain. However, if this finding is broadly used as a clinical test, treatment may be possible before too much damage is present, offering the hope of much better outcomes.

“This novel peptide is the long-sought surrogate marker for Alzheimer’s disease,” says lead researcher Masayasu Okochi, who works in the Department of Neuropsychiatry at Osaka University Graduate School of Medicine, Japan.

Treating Alzheimer’s disease is complex for a number of reasons. First, there are few or no signs that a person has the disease until the destructive process has been active in the person’s brain for many months or years. Second, once the damage is done in the brain, it is difficult to restore lost function.

Consequently, many people are trying to find ways of detecting the onset of Alzheimer’s disease long before any symptoms appear. In addition, they want to use a sampling method that does not involve costly scanning equipment.

The multi-centre Japanese team analysed CSF and brain tissue samples from people with and without diagnosis of Alzheimer’s disease. They discovered that increases in levels of their newly identified peptide (APL1beta28) reflected increased production of Abeta42 in the brain. While Abeta42 is always produced in the brain, this peptide is one of the key constituents of the senile plaques that play a critical role in Alzheimer’s disease, and increased production is associated with plaque formation.

“Many pharmaceutical companies are developing Abeta-targeting compounds that could prevent some of the brain damage associated with Alzheimer’s disease, but their use will be limited if given after symptoms appear. Our new test allows early diagnosis, giving patients the chance of getting maximum benefit from these new drugs,” says Okochi.

Full citation:
Yanagida.K, Okochi.M, et al. The 28-amino acid form of an APLP1-derived Abeta-like peptide is a surrogate marker for Abeta42production in the central nervous system. EMBO Mol. Med. 2009 1(4), 10.1002/emmm.200900026

About the Author

Masayasu Okochi (MD) is based at the Osaka University Graduate School of Medicine in Japan.

About the Journal

Molecular medicine is a rapidly-growing area of research at the interface between clinical research and basic biology. Powerful new analytical tools provided by molecular biology allow unprecedented insights into human physiology and the molecular basis of diseases. These insights are being translated into better diagnosis, prevention and patient care. EMBO Molecular Medicine is a peer-reviewed journal dedicated to the publication of original, cutting-edge research in the field of molecular medicine of interest to medical and basic scientists. The Journal publishes research articles and reviews highly relevant to all fields of clinical medicine and their related research areas in basic biology. Studies based on model organisms also fall within the scope of the journal, provided that the results presented are evidently relevant to human disease.

For more information please visit embomolmed.

Wiley-Blackwell’s business model for new journals

EMBO Molecular Medicine will be made freely available for the first two years of publication. Institutional customers can opt to receive complimentary online access for this journal. Institutions may also request one complimentary print subscription when registering for online access to EMBO Molecular Medicine.

About EMBO

The European Molecular Biology Organization (EMBO) promotes excellence in molecular life sciences by recognizing and fostering talented scientists, empowering them to advance the life sciences to understand how life works and share knowledge to help address the challenges of a changing world. For details about EMBO and its activities please visit embo.

Source
Wiley-Blackwell

M. D. Anderson, BCM, Launch Research Effort Targeting Asthma And Allergic Diseases

A new research alliance focuses on a molecular master switch suspected of igniting the inflammatory immune response that drives asthma and other allergic diseases.

The University of Texas M. D. Anderson Cancer Center and Baylor College of Medicine have launched the Texas Medical Center Asthma and Allergic Diseases Cooperative Research Center, funded by a $5.6 million five-year grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

“We can manage asthma, but there is no cure. Finding the cause of asthma is a fundamental question in immunology,” said principal investigator Yong Jun Liu, M.D., Ph.D., professor and chair of the Department of Immunology at M. D. Anderson. “The molecule we are studying, known as TSLP, appears to represent a very, very early trigger between allergens that find their way into the lungs and asthma.”

“This program is focused on trying to delineate the mechanisms by which viruses and allergens are able to initiate and drive the allergic response and progression of asthma,” said Dr. David Huston, professor of immunology at BCM , director of the college’s Biology of Inflammation Center, and co-principal investigator. “It’s probably the hottest area right now in the study of allergic diseases.”

The incidence and severity of asthma, a debilitating and potentially life-threatening constriction and inflammation of the airways, has increased over the past 20 years, with more than 155 million people affected in developed countries alone.

Earlier research by Liu established that inhalation of allergens, such as pollen or viruses, sets off production of TSLP in the lining of the lungs (epithelial cells) and by specialized cells known as mast cells. TSLP then launches a molecular cascade that results in overproduction of the immune system T cell known as Th2, a known culprit in the inflammation that causes chronic asthma.

“Th2 is an important, heavily studied T cell that causes asthma,” Liu said. “Our question is what induces and maintains Th2?”

By nailing down the details of this process, the investigators expect to generate new therapeutic targets for allergic disease and asthma. Liu expects drug development to begin late in the five-year grant period and extend beyond that.

The program is divided into four research efforts, starting with a project led by Huston that examines the mechanisms of TSLP expression by the epithelial and mast cells in human lungs.

Project two focuses on how TSLP then activates dendritic cells, key players in the immune system that engulf intruding antigens and present key portions of the intruder to T cells (Th2), which in turn help generate an antibody response. Li-yuan Yu-lee, Ph.D., professor of medicine at BCM, leads this project, on which Margie Moczygemba, Ph.D., assistant professor of medicine at BCM is co-investigator.

Project three, led by Liu, examines how the TSLP-generated dendritic cells in turn propagate Th2 effector and memory cells.

Project 4, led by Chen Dong, Ph.D., associate professor of immunology at M. D. Anderson, examines how inflammatory T helper cells then upregulate TSLP, perpetuating the inflammatory cycle.

Huston heads the project’s clinical research core, which includes Drs. Nick Hanania, Robert Atmar, Pedro Piedra, and Robert Couch, at BCM. Liu leads the analytical and administrative cores. All four research projects also will require close interaction, Liu said.

Steve Ziegler, Ph.D., director of the Immunology Program at the Benaroya Research Institute at Virginia Mason in Seattle, is co-investigator on projects 1 and 2. Ziegler is an expert on using mouse models to understand the biology of TSLP.

Immunological research at M. D. Anderson focuses on priming the immune system to identify and attack cancer cells. Inflammation also is involved in cancer development and growth, Liu said.

“In some cancers, the microenvironment that the tumor creates around itself looks like an allergic type of inflammation,” Liu said. “We need to understand this type of inflammation so we can design ways to block it in the tumor microenvironment, because it promotes tumor growth.

“While M. D. Anderson’s focus is not on allergies and asthma, Dr. Huston is one of the best physicians in the country for allergic disease and has a strong research program,” said Liu. “Our teams are complementary to each other’s expertise. This is an exciting cooperative program and both institutions will gain from this collaboration.”

In addition to several shared clinical and cancer-related research projects, this is the second major research collaboration established between M. D. Anderson and Baylor College of Medicine to study a disease other than cancer. In 2002, the two institutions formed the Bone Disease Program of Texas, which focuses on the study of osteoporosis and the treatment of bone disease.

The two institutions launched a joint neurosurgery program in June 2005, with Dr. Raymond Sawaya, M.D., chair of the of M. D. Anderson Neurosurgery Department for 15 years, also appointed chair of the Baylor College of Medicine Department.

Contact: Laura Madden-Fuentes of Baylor College of Medicine

Contact: Scott Merville

University of Texas M. D. Anderson Cancer Center

M. D. Anderson, BCM, Launch Research Effort Targeting Asthma And Allergic Diseases

A new research alliance focuses on a molecular master switch suspected of igniting the inflammatory immune response that drives asthma and other allergic diseases.

The University of Texas M. D. Anderson Cancer Center and Baylor College of Medicine have launched the Texas Medical Center Asthma and Allergic Diseases Cooperative Research Center, funded by a $5.6 million five-year grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

“We can manage asthma, but there is no cure. Finding the cause of asthma is a fundamental question in immunology,” said principal investigator Yong Jun Liu, M.D., Ph.D., professor and chair of the Department of Immunology at M. D. Anderson. “The molecule we are studying, known as TSLP, appears to represent a very, very early trigger between allergens that find their way into the lungs and asthma.”

“This program is focused on trying to delineate the mechanisms by which viruses and allergens are able to initiate and drive the allergic response and progression of asthma,” said Dr. David Huston, professor of immunology at BCM , director of the college’s Biology of Inflammation Center, and co-principal investigator. “It’s probably the hottest area right now in the study of allergic diseases.”

The incidence and severity of asthma, a debilitating and potentially life-threatening constriction and inflammation of the airways, has increased over the past 20 years, with more than 155 million people affected in developed countries alone.

Earlier research by Liu established that inhalation of allergens, such as pollen or viruses, sets off production of TSLP in the lining of the lungs (epithelial cells) and by specialized cells known as mast cells. TSLP then launches a molecular cascade that results in overproduction of the immune system T cell known as Th2, a known culprit in the inflammation that causes chronic asthma.

“Th2 is an important, heavily studied T cell that causes asthma,” Liu said. “Our question is what induces and maintains Th2?”

By nailing down the details of this process, the investigators expect to generate new therapeutic targets for allergic disease and asthma. Liu expects drug development to begin late in the five-year grant period and extend beyond that.

The program is divided into four research efforts, starting with a project led by Huston that examines the mechanisms of TSLP expression by the epithelial and mast cells in human lungs.

Project two focuses on how TSLP then activates dendritic cells, key players in the immune system that engulf intruding antigens and present key portions of the intruder to T cells (Th2), which in turn help generate an antibody response. Li-yuan Yu-lee, Ph.D., professor of medicine at BCM, leads this project, on which Margie Moczygemba, Ph.D., assistant professor of medicine at BCM is co-investigator.

Project three, led by Liu, examines how the TSLP-generated dendritic cells in turn propagate Th2 effector and memory cells.

Project 4, led by Chen Dong, Ph.D., associate professor of immunology at M. D. Anderson, examines how inflammatory T helper cells then upregulate TSLP, perpetuating the inflammatory cycle.

Huston heads the project’s clinical research core, which includes Drs. Nick Hanania, Robert Atmar, Pedro Piedra, and Robert Couch, at BCM. Liu leads the analytical and administrative cores. All four research projects also will require close interaction, Liu said.

Steve Ziegler, Ph.D., director of the Immunology Program at the Benaroya Research Institute at Virginia Mason in Seattle, is co-investigator on projects 1 and 2. Ziegler is an expert on using mouse models to understand the biology of TSLP.

Immunological research at M. D. Anderson focuses on priming the immune system to identify and attack cancer cells. Inflammation also is involved in cancer development and growth, Liu said.

“In some cancers, the microenvironment that the tumor creates around itself looks like an allergic type of inflammation,” Liu said. “We need to understand this type of inflammation so we can design ways to block it in the tumor microenvironment, because it promotes tumor growth.

“While M. D. Anderson’s focus is not on allergies and asthma, Dr. Huston is one of the best physicians in the country for allergic disease and has a strong research program,” said Liu. “Our teams are complementary to each other’s expertise. This is an exciting cooperative program and both institutions will gain from this collaboration.”

In addition to several shared clinical and cancer-related research projects, this is the second major research collaboration established between M. D. Anderson and Baylor College of Medicine to study a disease other than cancer. In 2002, the two institutions formed the Bone Disease Program of Texas, which focuses on the study of osteoporosis and the treatment of bone disease.

The two institutions launched a joint neurosurgery program in June 2005, with Dr. Raymond Sawaya, M.D., chair of the of M. D. Anderson Neurosurgery Department for 15 years, also appointed chair of the Baylor College of Medicine Department.

Contact: Laura Madden-Fuentes of Baylor College of Medicine

Contact: Scott Merville

University of Texas M. D. Anderson Cancer Center

Study Uncovers A Lethal Secret Of 1918 Influenza Virus

In a study of non-human primates infected with the influenza virus that killed 50 million people in 1918, an international team of scientists has found a critical clue to how the virus killed so quickly and efficiently.

Writing this week (Jan. 18, 2007) in the journal Nature, a team led by University of Wisconsin-Madison virologist Yoshihiro Kawaoka reveals how the 1918 virus – modern history’s most savage influenza strain – unleashes an immune response that destroys the lungs in a matter of days, leading to death.

The finding is important because it provides insight into how the virus that swept the world in the closing days of World War I was so efficiently deadly, claiming many of its victims people in the prime of life. The work suggests that it may be possible in future outbreaks of highly pathogenic flu to stem the tide of death through early intervention.

The study “proves the 1918 virus was indeed different from all of the other flu viruses we know of,” says Kawaoka, a professor in the UW-Madison School of Veterinary Medicine and at the University of Tokyo.

The new study, conducted at the Public Health Agency of Canada’s National Microbiology Laboratory in Winnipeg, Manitoba, utilized the 1918 flu virus, which has been reconstructed by researchers using genes obtained from the tissues of victims of the great pandemic in a reverse genetics process that enables scientists to make fully functioning viruses.

“In 1918, the existence of viruses had barely been recognized. In fact, the influenza virus wasn’t identified until 1933. Thanks to recent technological advancements, we are now able to study this virus and how it wreaked havoc around the globe,” explains Darwyn Kobasa, research scientist with the Public Health Agency of Canada and lead author of the new study. “This research provides an important piece in the puzzle of the 1918 virus, helping us to better understand influenza viruses and their potential to cause pandemics.”

By infecting monkeys with the virus, the team was able to show that the 1918 virus prompted a deadly respiratory infection that echoed historical accounts of how the disease claimed its victims.

Importantly, the new work shows that infection with the virus prompted an immune response that seems to derail the body’s typical reaction to viral infection and instead unleashes an attack by the immune system on the lungs. As immune cells attack the respiratory system, the lungs fill with fluid and victims, in essence, drown. The mechanisms that contribute to the lethality of the virus were uncovered by University of Washington researchers using functional genomics, a technique in which researchers analyze the gene functions and interactions. Learning more about the virulence mechanisms of the 1918 flu virus may help researchers understand how to keep the virus from causing such a severe immune response.

“This study in macaques, combined with our earlier research showing the host response in mice infected with the 1918 flu, suggests that the host immune response is out of control in animals infected with the virus,” said Michael G. Katze, professor of microbiology at the University of Washington in Seattle, who led the functional genomics portion of the new study and led the previous mouse-based study. “Our analysis revealed potential mechanisms of virulence, which we hope will help us develop novel antiviral strategies to both outwit the virus and moderate the host immune response.”

The same excessive immune reaction is characteristic of the deadly complications of H5N1 avian influenza, the strain of bird flu present in Asia and which has claimed nearly 150 human lives but has not yet shown a capacity to spread easily among people.

“What we see with the 1918 virus in infected monkeys is also what we see with H5N1 viruses,” Kawaoka says, suggesting that the ability to modulate immune response may be a shared feature of the most virulent influenza viruses.

In the new study, conducted in a high-level biosafety laboratory (BSL 4) at the Public Health Agency of Canada’s National Microbiology Laboratory, seven primates were infected with the reconstructed 1918 virus. Clinical signs of disease were apparent within 24 hours of infection and within eight days euthanization was necessary. The rapid course of the disease mirrors how quickly the disease ran its course in its human victims in 1918.

Upon infection, the virus grew rapidly in the infected animals, suggesting the agent somehow sets the stage for virulent infection: “Somehow, early in infection, this virus does something to the host that allows it to grow really well,” says Kawaoka. “But we don’t know what that is.”

Knowing that the virus does something early in infection to trigger such a devastating immune response may provide biomedical researchers with clues about how to intervene and stop or mitigate the virus’ potentially lethal effects, Kawaoka says.

“Things may be happening at an early time point (in infection), but we may be able to step in and stop that reaction.”

In addition to Kawaoka, authors of the new Nature paper include Darwyn Kobasa, Steven M. Jones, Hideki Ebihara, Friederike Feldman, Judie B. Alimonti, Lisa Fernando, Yan Li and Heinz Feldman of Canada’s National Microbiology Laboratory; Kyoko Shinya of Japan’s Tottori University; John C. Kash and Michael G. Katze of the University of Washington; John Copps of the Canadian Food Inspection Agency’s National Centre for Foreign Animal Disease; and Yasuko Hatta, Jin Hyun Kim, Peter Halfmann and Masato Hatta of UW-Madison.

The new study was supported by the Public Health Agency of Canada, the Japanese Ministries of Education, Culture, Sports, Science and Technology, and private grants to Kawaoka. – Terry Devitt.

Contact: Yoshihiro Kawaoka

University of Wisconsin-Madison